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Effects of iguratimod on the levels of circulating regulators of bone remodeling and bone remodeling markers in patients with rheumatoid arthritis

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Abstract

This study aims to investigate the effect of iguratimod, a novel disease-modifying antirheumatic drug, alone or combined with methotrexate (MTX), on the serum levels of regulators of bone remodeling (receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), and Dickkopf-1 (DKK-1)) and bone remodeling markers (C-telopeptide of type I collagen (CTX-I) and procollagen type I N-terminal propeptide (PINP)) in patients with rheumatoid arthritis (RA). Patients with RA were treated with iguratimod, MTX, or their combination for 12 months. Serum samples were collected before treatment and 6 and 12 months afterwards. RANKL, OPG, DKK-1, CTX-I, and PINP levels were measured, and radiographic progression was assessed. The serum RANKL levels decreased after treatment for 6 and 12 months with iguratimod (median: baseline 565.00 pmol/L vs. 6 months 411.00 pmol/L vs. 12 months 212.00 pmol/L), MTX (median: baseline 562.50 pmol/L vs. 6 months 399.50 pmol/L vs. 12 months 163.50 pmol/L), and their combination (median: baseline 971.00 pmol/L vs. 6 months 272.50 pmol/L vs. 12 months 241.50 pmol/L). Combination therapy showed greater effects 6 months post-treatment compared to single-drug therapy. PINP levels increased significantly 12 months post-treatment with all therapies, but only the combination therapy led to decreased CTX-I levels. OPG and DKK-1 levels showed no significant changes. The three treatments showed no significant differences in radiographic progression. Iguratimod could stimulate bone formation and regulate the RANKL/RANK/OPG system rather than DKK-1levels. Its effects are comparable to those of MTX, and combination therapy showed stronger effects.

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Acknowledgements

This study was supported by grants from the Science and Technology Ministry “12th Five-Year Plan” to support science and technology of China (No. 2014BAI07B00). We thank Professor Bo Li and Professor Pinghui Sun from the Department of Epidemiology and Biostatistics, Jilin University School of Public Health for assistance with statistical analysis. We also appreciate the anonymous referees for their valuable suggestions and questions.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun, 130033, China

    Xuetong Wang, Cuili Ma, Ping Li, Feng Zhao & Liqi Bi

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  1. Xuetong Wang
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  2. Cuili Ma
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  3. Ping Li
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  4. Feng Zhao
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Correspondence to Liqi Bi.

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Wang, X., Ma, C., Li, P. et al. Effects of iguratimod on the levels of circulating regulators of bone remodeling and bone remodeling markers in patients with rheumatoid arthritis. Clin Rheumatol 36, 1369–1377 (2017). https://doi.org/10.1007/s10067-017-3668-8

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  • DOI: https://doi.org/10.1007/s10067-017-3668-8

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